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Ethanolic Leaf Extract of Aloe Barbadensis (Aloe Vera) Mitigates
Mercury Induced Alzheimer Like Symptoms on Basal Ganglia of
Albino Wistar Rats
Ezeani, J.O
1
, Nwakanma, A.A
2*
, Elemuo, S.C
3
, Anyiam, K.E
4
1 2 3 4
Department of Human Anatomy,Chukwuemeka Odumegwu Ojukwu University, Uli Campus,
Anambra State,Nigeria
*Corresponding Author
DOI: https://doi.org/10.51584/IJRIAS.2025.10100000154
Received: 09 October 2025; Accepted: 16 October 2025; Published: 18 November 2025
ABSTRACT
Mercury exposure has been linked with numerous neurological disorders that frequently trigger Alzheimer’s
disease through oxidative stress processes. This study aims to determine the ameliorative potential of Aloe
barbadensis on mercury induced Alzheimer- like symptoms on basal ganglia of wistar rats. Thirty-five wistar
rats with average weight 150g were randomly divided into five groups designated A-E with seven rats per group.
Group A served as the control and did not receive any treatment, group B received 5mg/kg mercury chloride
only for three weeks, group C received 500mg/kg of ethanolic extract of Aloe barbadensis for 3 weeks, groups
D and E received 5mg/kg of mercury chloride for 3 weeks followed by 250mg/kg and 500mg/kg of ethanolic
extract of Aloe barbadensis for 3 weeks respectively. All administrations were via oral gavage. Anxiety index
and recognition memory were evaluated using open field and novel object recognition tests. Blood was obtained
via ocular puncture for serum estimation of superoxide dismutase (SOD), malondialdehyde (MDA) levels. Brain
tissue obtained were homogenized for estimation of Acetylcholinesterase (AChE) and glutamate levels and also
processed for routine Hematoxylin and eosin and silver Beilschowsky staining. Results of the neurobehavioural
tests showed significant (P<0.05) increase in anxiety indexwhen comparand significant decrease (P<0.05) in
recognition index in group B. There was significant (P<0.05) decrease in SOD, AChE, glutamatelevels in group
B compared with groups A, C, D and E while there was a significant increase (P<0.05) in MDA levels in group
B. Histological study of the basal ganglia showed pyknotic nuclei in group B while silver beilschowsky stain
revealed amyloid plaques deposition in group B. These results revealed that mercury chloride caused oxidative
stress, anxiety, reduced AChE and glutamate levels, pyknosis and deposition of amyloid plaques on the basal
ganglia and Aloe Barbadensis ethanolic extract mitigated these effects and may be useful in the management of
Alzheimer like symptoms.
Keywords Mercury chloride, oxidative stress, amyloid plaques, Alzheimer’s disease, Aloe barbadensis
INTRODUCTION
Environmental exposure to toxic chemicals has been strongly associated with neurotoxicity, particularly through
mechanisms involving oxidative stress and lipid peroxidation in brain tissues. Among these environmental
pollutants, mercury chloride (HgCl₂) is a well-known neurotoxicant that affects the central nervous system and
has been implicated in the development of several neurological disorders [7], including Parkinson’s disease,
Alzheimer’s disease and Huntington’s disease. Mercury, a heavy metal of global concern is introduced into the
ecosystem through both natural and anthropogenic activities, leading to its persistence and bioaccumulation in
humans and animals. Due to its unique physicochemical properties, mercury deeply affects human health and
has been linked to cognitive dysfunction and other neurological disorders related to neuroinflammation and
oxidative stress processes [5], resulting in neuropathological diseases such as Alzheimer’s disease and other
neurodegenerative diseases.
Alzheimer's disease is a multifactorial neurological condition associated with neuropathological and
neurobehavioral changes, including cognition and memory loss [12]. The basal ganglia an essential brain region
is associated with reward, cognition and motor control. It acts as the gate-keeping mechanism for motor
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movement initiation [15], deciding which actions to execute or inhibit. It is a primary site of dysfunction in both
Parkinson’s disease and Huntington’s disease.
Increasing research indicates that mercury-related neurotoxicity may compromise the functional integrity of the
basal ganglia. Given this region's critical involvement in both motor and cognitive functions, it is vital to explore
how mercury exposure affects its neuronal health, particularly in relation to Alzheimer’s disease-like symptoms.
The pathogenesis of mercury-induced neurotoxicity is primarily associated with oxidative stress, leading to
neuronal damage, neurotransmitter imbalances and cognitive deficits characteristic of Alzheimer’s disease.
Oxidative stress disrupts the delicate balance of antioxidants, such as superoxide dismutase (SOD) and elevates
lipid peroxidation markers, including malondialdehyde (MDA). It also impairs enzymes critical for neural
function, including acetylcholinesterase (AChE). Additionally, mercury accumulation contributes to
pathological changes such as neuronal pyknosis and amyloid plaque deposition, which are hallmarks of
Alzheimer’s pathology. Thus, Alzheimer's disease is linked to dementia, characterized by chronic behavioral
changes such as apathy, aggressiveness, depression, and lack of social activities [23].
Antioxidants play a vital role in reducing oxidative stress markers linked to reactive oxygen species formation.
In recent years, natural antioxidants have attracted attention for their neuroprotective properties against heavy
metal-induced neurotoxicity. Medicinal plants are increasingly recognized for their potent antioxidant properties,
which contribute significantly to their therapeutic value in addressing a diverse array of health conditions,
including neurodegenerative disorders like Alzheimer’s disease and other neurological impairments ([20],[27]).
These plants are rich in bioactive phytochemicalssuch as flavonoids, alkaloids, terpenoids and polyphenols
that not only neutralize harmful free radicals but also modulate key biological pathways involved in
inflammation, immune response, and cellular repair.
Their multifaceted healing potential stems from a synergistic blend of pharmacological actions. Anti-
inflammatory compounds help reduce neuroinflammation, a hallmark of many brain disorders. Antioxidants
protect neurons from oxidative stress, which is implicated in the progression of Alzheimer’s and Parkinson’s
diseases. Immunomodulatory agents enhance the body’s defense mechanisms, while anticancer and
antimicrobial constituents broaden their application to oncology and infectious disease management [19].Beyond
their biochemical effects, medicinal plants offer a holistic approach to healing, often aligning with traditional
medicine systems that emphasize balance and restoration. As interest grows in natural and integrative therapies,
these plants continue to be explored not only for symptom relief but also for their potential to slow disease
progression and improve quality of life in chronic neurological conditions.
Aloe barbadensis miller (Aloe vera) has demonstrated potential in mitigating oxidative damage and improving
neurological outcomes in various experimental models. It is a perennial green herb native to North Africa, the
Middle East, Southern Mediterranean, and Canary Islands [22]. Aloe barbadensis contains active compounds
such as aloe-emodin, aloin, aloesin, emodin, and acemannan, linked to pharmacological effects like anticancer,
antioxidant, antidiabetic and antihyperlipidemic actions ([8],[14]).
This study investigates whether the ethanolic leaf extract of Aloe barbadensis (Aloe vera) can counteract the
neurodegenerative effects of mercury chloride exposure, which is known to induce Alzheimer-like symptoms in
the basal ganglia of albino Wistar rats. Mercury chloride is a potent neurotoxin that disrupts neuronal function
primarily through oxidative stress, leading to behavioral impairments, biochemical imbalances, and structural
brain damage that resemble the pathology of Alzheimer’s disease.
To address this, the study evaluates the extent to which Aloe barbadensis extract can restore normal brain
function by targeting key markers of neurotoxicity. These include behavioral parameters such as anxiety and
memory performance, assessed through open field and novel object recognition tests. On a biochemical level,
the research measures antioxidant enzyme activity (superoxide dismutase), lipid peroxidation (malondialdehyde)
and neurotransmitter-related enzymes (acetylcholinesterase and glutamate), which are critical indicators of
oxidative stress and synaptic integrity.
Additionally, the study examines histopathological changes in the basal ganglia, focusing on neuronal
degeneration (evidenced by pyknotic nuclei) and the presence of amyloid plaques, which are hallmark features
of Alzheimer’s disease. By comparing treated and untreated groups, the research aims to determine whether Aloe
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barbadensis can mitigate these effects, thereby offering a potential natural therapeutic strategy for managing
mercury-induced neurodegeneration and Alzheimer-like conditions.
MATERIALS AND METHODS
Experimental animals
The study was conducted in the animal house unit, Department of Human Anatomy, Faculty of Basic medical
Sciences, Chukwuemeka Odumegwu University, Uli campus. With 35 adult male wistar rats weighing 130
150g.The rats were kept in standard cages at room temperature of 27±2°C and was maintained on 12-hours light
and dark cycles to maintain the normal circadian rhythm fed with standardized pellet grower’s feed and distilled
water ad libitum. The rats were acclimatized for two weeks for physiological adaptation to the animal house
before administering mercury chloride and ethanol extracts of Aloe barbadensis miller.
Plant extract preparation
Aloe barbadensis miller (Aloe-vera) was obtained from a local farm in Nnewi North and was washed to remove
dirt. The dried aloe-vera was milled into a coarse powdered form using a local grinder. About 250 g each of the
dried forms of the aloe-vera was macerated in 1000 ml of 95% absolute ethanol for 48 hours. It was filtered using
a clean white cloth and further filtration using Whatman No 1 filter paper. The filtrate was concentrated using a
rotatory evaporator and dried further using a laboratory oven at 45ºC into a gel-like form. The extract was
preserved in airtight container and kept in a refrigerator for further usage.The extraction method was done with
modifications as described according to the method employed by [1].
Ethical Approval
This was obtained from the ethical committee, faculty of basic medical sciences Chukwuemeka Odumegwu
Ojukwu University, Uli campus in compliance with the relevant laws and institution’s guidelines.
All authors hereby declare that "Principles of laboratory animal care" (NIH publication No. 85-23, revised 1985)
were followed, as well as specific national laws where applicable. All experiments have been examined and
approved by the appropriate ethics committee.
Subacute Toxicity Study
All animals were housed under same environmental conditions throughout the study. Thirty-five rats were
randomly assigned into five groups (n = 7). Group A served as the negative control and received feed and water
only. Group B, received 5 mg/kg of mercury chloride for 3 weeks. Group C was administered 500 mg/kg of Aloe
barbadensis extract for 3 weeks. Group D and E received 5 mg/kg of mercury chloride for 3 weeks, followed by
250 mg/kg and 500mg/kg of Aloe barbadensis extract for another 3 weeks respectively. All administrations were
done daily via oral gavage.
Twenty-four hours after the final treatment, animals were subjected to open field test followed by object
recognition test. Blood was collected via ocular puncture. Serum was separated and used for superoxide
dismutase and malondialdehyde assays. The animals were anesthetized using 50mg/kg ketamine.Brain tissue
obtained were homogenized for estimation of Acetylcholinesterase (AChE) and glutamate levels and also
processed for routine Hematoxylin and eosin and silver Beilschowsky staining.
Statistical Analysis
Data were analyzed using GraphPad Prism version 9.5.1. One-way ANOVA followed by Fisher’s Least
Significant Difference (LSD) post hoc test was used to analyze brain levels of MDA, SOD, glutamate,
acetylcholinesterase activity, anxiety index, and recognition memory. Histological findings, including amyloid
plaque deposition, were also evaluated descriptively. Results were expressed as mean ± standard error of the
mean (SEM), and differences were considered statistically significant at p ≤ 0.05.
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RESULTS
Figure 1: Effect of ethanolic extract of Aloe barbadensis Miller on anxiety index following mercury chloride
exposed rats.
A B C D E
0.0
0.5
1.0
1.5
Anxiety Index
Anxiety index results showed that there was a significant increase (P<0.05) in anxiety index in group B compared
to group A and the aloe barbadensis treated groups while there was a decrease in anxiety index in group C
compared with group A. Figure 1
Figure 2: Effect of ethanolic extract of Aloe barbadensis Miller on recognition index following mercury chloride
exposed rats.
A B C D E
0.0
0.2
0.4
0.6
0.8
Recognition index
Results of the recognition index showed that there was a significant increase(P<0.05) in recognition index in
groups C, D and E compared with groups A and B while there was no significant difference between the
recognition index of group B compared with group A. Figure 2
Figure 3: Effect of ethanolic extract of Aloe barbadensis Miller on SOD level following mercury chloride
exposed rats.
A B C D E
0
5
10
15
20
SOD level (U/l)
SOD levels in group B had a significant decrease(P<0.05). Groups C, D, and E had a significant increase
compared to group A. However, the serum SOD activities in groups C, D, and E had a significant increase
compared to group B. Figure 3
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Figure 4: Effect of ethanolic extract of Aloe barbadensis Miller on MDA level following mercury chloride
exposed rats.
A B C D E
0.0
0.5
1.0
1.5
2.0
MDA level (nm/mol)
Result shows a significant increase (p<0.05) in the MDA level in group B while groups C,D,E showed a decrease
when compared to group A. Figure 4
Figure 5:Effect of ethanolic extract of Aloe barbadensis Miller on AchE level following mercury chloride
exposed rats.
The acetylcholine esterase activity reveals significant increase (p<0.05) in the AChE activity in groups C, D, and
E compared to group B. While group C had no significant difference compared to group A. Figure. 5
Figure 6: Effect of ethanolic extract of Aloe barbadensis Miller on glutamate level following mercury chloride
exposed rats.
A B C D E
0.0
0.5
1.0
1.5
Glutamate level (mIU/mL)
Result reveals a decrease in the glutamate level in group B and E, groups C and D had an increase when compared
to group A, which had significant difference in group B(P<0.05). However, the glutamate level shows a
significant increase in groups C and D(P<0.05). Group E had no significant difference compared to group B.
Figure 6
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Histological Studies Results
Hematoxylin and Eosin (H &E) staining
Figure 7: Group A (H&E staining)
Group A received feed and water ad libitum: Photomicrograph of basal ganglia show some densely packed
medium neurons (N), mainly caudate and putamen (collectively known as the striatum). Elsewhere, there are
numerous glial cells (GC). The background matrix shows a dense neuropil (NP). H & E (x400). Figure 7
Figure 8: Group B (H&E staining)
Group B received 5mg/kg of mercury chloride. A photomicrograph section of the basal ganglia shows pyknotic
nuclei with moderate reduction of neurons (N) and the glial cells. H & E (x400). Figure 8
Figure 9: Group C (H&E staining)
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Group C (500 mg/kg of Ethanolic extract ofaloe barbadensis): A photomicrograph section of the basal ganglia
showing numerous large neurons (N) and the glial cells. Stained with H & E (x400). Figure 9
Figure 10: Group D (H&E staining)
Group D (5mg/kg of HgCl2 for 3-weeks + 250 mg/kg of Ethanolic extract of aloe barbadensis): A
photomicrograph section of the Basal ganglia shows moderate reduction of neurons (N) and the glial cells.
Stained with H & E (x400). Figure 10
Figure 11: Group E (H&E staining)
Group E (5mg/kg of HgCl2 for 3-weeks + 500 mg/kg of Ethanolic extract ofaloe barbadensis): Photomicrograph
section of the Basal ganglia showing normal neurons (N) and glial cells. Stained with H & E (x400). Figure 11
Silver Beilschowsky Stain
Figure 12: Group A (Silver Beilschowsky Stain).
Group A received feed and water ad libitum: A section of brain (Basal ganglion) section of albino rat showing
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negative staining of the neurofibrillary tangle and senile plaques (BielschowskyX400). Figure 12
Figure 13: Group B (Silver Beilschowsky Stain).
Group B (5mg/kg of HgCl2): A section of brain (Basal ganglion) section of albino rat shows negative staining
of the neurofibrillary tangle and mild positive staining of the senile plaques (arrow) (Bielschowsky X400). Figure
13
Figure 14: Group C (Silver Beilschowsky Stain).
Group C (500 mg/kg of Ethanolic extract of aloe barbadensis): A section of brain (Basal ganglion) section of
albino rat shows negative staining of the neurofibrillary tangle senile plaques (Bielschowsky X400). Figure 14
Figure 15: Group D (Silver Beilschowsky Stain).
Group D (5mg/kg of HgCl2 for 3-weeks + 250 mg/kg of Ethanolic extract of aloe barbadensis): A section of
brain (Basal ganglion) section of albino rat shows negative staining of the neurofibrillary and Senile plaques
(Bielschowsky X400). Figure 15
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Figure 16: Group E (Silver Beilschowsky Stain).
Group E (5mg/kg of HgCl2 for 3-weeks + 500 mg/kg of Ethanolic extract of aloe barbadensis): A section of
brain (Basal ganglion) section of albino rat showing negative staining of the neurofibrillary tangle and negative
staining of the Senile plaques (BielschowskyX400). Figure 16
DISCUSSION
The primary objective of this research was to assess the ameliorative effects of ethanolic leaf extract from Aloe
barbadensis (Aloe vera) against the neurotoxic impact of mercury chloride, which is known to provoke
Alzheimer-like symptoms in the basal ganglia of albino Wistar rats. Mercury chloride, identified as a hazardous
environmental pollutant, interferes with brain function by promoting oxidative stress and cellular damage
([17],[18]). Its neurotoxicity manifests through behavioral disturbances, biochemical disruptions, and structural
degeneration that resemble Alzheimer’s disease pathology[18]. Given the therapeutic promise of plant-based
compounds, Aloe barbadensis, rich in antioxidants like aloin, aloe-emodin, and ace Mannan, was selected for its
potential to counteract these effects ([20],[6]). This study explored its influence on anxiety and memory behavior,
oxidative stress markers, neurotransmitter levels, and histological changes in brain tissue, aiming to establish its
role as a natural intervention for mercury-induced neurodegeneration.
Neurobehavioral assessments evaluates motor, sensory, and cognitive function[11]. The neurobehavioral
outcomes of this study offer compelling evidence of the impact of mercury chloride on brain function and the
therapeutic potential of Aloe barbadensis in reversing these effects. Two behavioral paradigmsopen field test
and novel object recognition testwere employed to assess anxiety levels and recognition memory,
respectively.Mercury chloride, a known neurotoxin, significantly elevated anxiety levels in rats, as evidenced by
the open field test. Rats in Group B, which received mercury chloride alone, exhibited a marked increase in
anxiety index compared to both the untreated control group and those treated with Aloe barbadensis. This
behavioral alteration aligns with established literature indicating that mercury disrupts neurotransmitter systems
and induces oxidative stress, particularly in brain regions responsible for emotional regulation ([17],[18]).
Interestingly, Group C, which received only Aloe barbadensis extract without mercury exposure, demonstrated
a significant reduction in anxiety index relative to the control group. This suggests that the extract may possess
intrinsic anxiolytic properties, potentially mediated by its rich phytochemical compositionincluding
polysaccharides, flavonoids, and anthraquinoneswhich are known to modulate oxidative pathways and
neuroinflammation ([6]; [16]). The anxiolytic-like effects observed in the Aloe-treated groups (D and E) further
support the hypothesis that Aloe barbadensis can counteract mercury-induced emotional disturbances.
In the novel object recognition test, which assesses recognition memory, rats in Groups C, D, and E exhibited
significantly higher recognition indices than both the control and mercury-only groups. This enhancement in
memory performance suggests that Aloe barbadensis not only protects against cognitive deficits induced by
mercury but may also enhance baseline cognitive function. These findings are consistent with previous studies
that attribute memory-enhancing effects of Aloe-based formulations to their antioxidant and anti-inflammatory
actions, which help preserve synaptic integrity and neurotransmitter balance ([25],[20]).
Notably, there was no significant difference in recognition index between the mercury-only group (Group B)
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and the control group (Group A), indicating that the duration or dosage of mercury exposure may have had a
more pronounced effect on anxiety-related behavior than on recognition memory within the study’s timeframe.
Nevertheless, the cognitive improvements observed in the Aloe-treated groups reinforce the extract’s
neuroprotective potential. These results suggest that Aloe barbadensis may exert its effects by restoring redox
balance, enhancing cholinergic function, and reducing neuronal damagemechanisms that are crucial in the
context of neurodegenerative conditions such as Alzheimer’s disease ([24],[6]).
The biochemical results from this study highlight the oxidative stress and neurochemical disruptions caused by
mercury chloride, as well as the restorative effects of Aloe barbadensis extract. Mercury chloride exposure led
to a marked reduction in SOD activity in Group B, indicating weakened antioxidant defenses and heightened
oxidative stress. This aligns with previous studies by [17] and [18], which reported that mercury compounds
impair enzymatic antioxidant systems in the brain. In contrast, Groups C, D, and Etreated with Aloe
barbadensisshowed significantly elevated SOD levels compared to both the control and mercury-only groups.
This suggests that the extract enhances antioxidant enzyme activity, likely due to its bioactive compounds such
as flavonoids and polysaccharides ([20], [6]).
MDA levels were significantly higher in Group B, confirming the presence of lipid peroxidation and oxidative
damage. Although Groups C, D, and E showed reduced MDA levels compared to Group A, these differences
were not statistically significant. However, the significant reduction in MDA levels compared to Group B
indicates that Aloe barbadensis effectively counteracts mercury-induced oxidative stress, consistent with
findings by [24] and [26], who demonstrated the extract’s ability to protect neuronal membranes from oxidative
injury.
AChE activity was notably reduced in Group B, reflecting impaired cholinergic transmissiona hallmark of
Alzheimer-like neurodegeneration. Mercury’s interference with neurotransmitter systems has been documented
to affect memory and learning processes[18]. Groups D and E showed a significant increase in AChE activity
compared to both Group A and Group B, while Group C showed an increase that was not statistically significant.
Rats in (Group B) exposured to mercury chloride showed a significant reduction in glutamate levels, indicating
impaired excitatory neurotransmission and potential excitotoxic damage. This finding is consistent with previous
research by [24] and [2], which demonstrated that mercury disrupts glutamate transport and contributes to
neuronal dysfunction. In contrast, rats in (Groups C and D) treated with
Aloe barbadensis extract showed increased glutamate levels compared to the control group, suggesting that
Aloe plays a role in restoring glutamatergic balance. This aligns with the findings of [3], who showed that Aloe
exhibits neuroprotective effects against glutamate-induced toxicity. However, Group E, which received mercury
and a high dose of Aloe, did not show significant improvement, possibly due to dose-dependent modulation or
saturation of Aloe's effect. As noted by [6], higher concentrations of Aloe may have different effects on
neurotransmitter dynamics, warranting further investigation. These results suggest that Aloe barbadensis may
help restore cholinergic function, particularly when administered after mercury exposure. Its neuroprotective
effect may be attributed to its ability to reduce oxidative stress and preserve neuronal integrity ([6],[16]).
Histological Observations
H&E Staining of the Basal Ganglia
The histological assessment of the basal ganglia using hematoxylin and eosin (H&E) staining revealed distinct
cellular alterations across the experimental groups, offering valuable insight into the neurotoxic effects of
mercury chloride and the restorative potential of Aloe barbadensis extract.
Group A (Control Feed and Water ad libitum) - Tissue sections from the control group displayed well-preserved
neural architecture. The basal ganglia, particularly the caudate and putamen regions, showed a dense population
of medium-sized neurons with clearly defined nuclei. Surrounding these neurons were numerous glial cells,
including astrocytes and oligodendrocytes, embedded within a richly textured neuropil composed of dendrites,
axons, and synaptic terminals. This intact histological profile reflects a healthy and functional neural
environment, consistent with normal striatal morphology described in neuroanatomical literature [13].
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Group B (Mercury Chloride 5 mg/kg)- Sections from rats exposed to mercury chloride revealed significant
histopathological alterations. There was a moderate reduction in neuronal and glial cell populations,
accompanied by the presence of pyknotic nucleiindicative of chromatin condensation and early neuronal
death. These changes are characteristic of mercury-induced neurotoxicity, which disrupts mitochondrial function
and promotes oxidative stress, leading to apoptosis and neuroinflammation [24]. The damage observed in the
basal ganglia underscores mercury’s affinity for sulfhydryl groups in neuronal proteins, impairing cellular
metabolism and structural integrity.
Group C (Aloe barbadensis Extract 500 mg/kg) -Histological sections from rats treated with Aloe barbadensis
extract alone showed a robust population of large, healthy neurons and glial cells. The preservation of cellular
architecture suggests that the extract may enhance neuronal resilience or support neurogenesis. These effects are
likely mediated by the plant’s bioactive compoundssuch as aloin, aloe-emodin, and acemannanwhich
possess antioxidant and anti-inflammatory properties that stabilize neural membranes and reduce oxidative
burden [6].
In group D (Mercury + Aloe barbadensis 250 mg/kg), the basal ganglia exhibited moderate neuronal and glial
cell loss. While the damage was less severe than in the mercury-only group, it was still evident, indicating partial
neuroprotection. The reduced efficacy at this lower dose suggests a dose-dependent relationship between Aloe
barbadensis administration and its neuroprotective capacity. This finding aligns with previous studies showing
that higher concentrations of plant-derived antioxidants are more effective in counteracting heavy metal-induced
neuronal damage [13].
Group E (Mercury + Aloe barbadensis 500 mg/kg) - Sections from this group revealed normal neuronal and
glial populations, suggesting a more substantial protective effect than observed in Group D. The improved
histological profile supports the hypothesis that higher doses of Aloe barbadensis offer enhanced
neuroprotection, likely through increased antioxidant enzyme activity and reduced lipid peroxidation. These
findings are consistent with [24] and [6], who reported that plant-based antioxidants can significantly mitigate
mercury-induced neurodegeneration when administered at therapeutic levels.
The H&E staining results clearly demonstrate the neurotoxic impact of mercury chloride on the basal ganglia,
characterized by neuronal shrinkage, pyknotic nuclei, and glial cell loss. Treatment with Aloe barbadensis
extract, particularly at 500 mg/kg, showed substantial histological improvement, reinforcing its role as a
neuroprotective agent. These findings are consistent with literature highlighting the extract’s antioxidant, anti-
inflammatoryand neurorestorative properties, making it a promising plant for mitigating heavy metal-induced
neurodegeneration.
Silver Bielschowsky Staining of the Basal Ganglia
Silver Bielschowsky staining is a specialized technique used to detect hallmark features of neurodegeneration,
particularly neurofibrillary tangles (NFTs) and senile plaquesboth of which are closely associated with
Alzheimer’s disease pathology. The staining patterns observed across the experimental groups in this study
provide valuable insight into the extent of mercury-induced damage and the neuroprotective effects of Aloe
barbadensis Miller.
Group A (Control) -Brain sections from the control group revealed negative staining for neurofibrillary tangles
and no evidence of senile plaque formation. The absence of sparse tangles and plaques indicates preserved neural
integrity in the basal ganglia [13].
Group B (Mercury Chloride Only) -Sections from rats exposed to mercury chloride showed a reversal in staining
patternno detectable neurofibrillary tangles but mild positive staining for senile plaques. This indicates that
mercury exposure may accelerate amyloid plaque formation while disrupting tau protein aggregation pathways.
Mercury’s neurotoxicity is known to promote oxidative stress and protein misfolding, contributing to the
deposition of amyloid material in brain regions critical for cognition and motor control ([24],[18]).
In rats treated with Aloe barbadensis extract alone, both neurofibrillary tangles and senile plaques were absent.
This clean histological profile suggests that the extract may prevent age-related neurodegenerative changes and
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maintain neuronal health. The absence of pathological markers supports the extract’s antioxidant and anti-
inflammatory properties, which help preserve protein stability and prevent oxidative damage [6].
Group D (Mercury + 250 mg/kg Aloe barbadensis) -Sections from this group also showed no staining for either
neurofibrillary tangles or senile plaques, indicating that even a moderate dose of Aloe barbadensis was effective
in preventing mercury-induced neurodegeneration. This suggests that the extract may inhibit both amyloid
deposition and tau pathology, possibly by enhancing antioxidant defenses and modulating inflammatory
responses [20].
In group E, negative staining for neurofibrillary tangles and senile plaques was observed. Compared to group B,
this pattern reflects complete protection, with the higher dose of Aloe barbadensis effectively suppressing plaque
formation. This outcome supports the dose-dependent efficacy of the extract and its ability to
reduceneurofibrillary pathology under toxic conditions [25].
The Silver Bielschowsky staining results demonstrate that mercury chloride promotes senile plaque formation
in the basal ganglia, while Aloe barbadensis extractespecially at higher dosescan effectively prevent or
reduce these neurodegenerative markers. These findings reinforce the therapeutic potential of Aloe barbadensis
in protecting against heavy metal-induced brain damage and Alzheimer-like pathology.
The outcomes of this study reaffirm the well-documented neurotoxic effects of mercury chloride, which include
oxidative stress, neurotransmitter disruption, and structural damage to brain tissue. Behavioral deficits,
biochemical imbalances, and histological abnormalities observed in mercury-treated rats align with previous
research showing that mercury exposure leads to neuronal death, lipid peroxidation, and glial cell depletion
particularly in the basal ganglia, a region vital for motor coordination and cognitive processing ([24],[18]). The
behavioral impairments observed in mercury-exposed rats, including heightened anxiety and diminished
recognition memory, reflect symptoms commonly seen in the early stages of Alzheimer’s disease. These deficits
are associated with disruptions in neurotransmitter systems, particularly the cholinergic pathways, alongside
increases in oxidative stress indicators such as malondialdehyde (MDA). Histological evidence of senile plaques
further substantiates the pathological similarity to Alzheimer’s disease [9].
Remarkably, administration of Aloe barbadensis extract significantly counteracted these adverse effects. Treated
rats demonstrated reduced anxiety, enhanced memory performance, increased levels of superoxide dismutase
(SOD), lowered malondialdehyde (MDA), and normalized acetylcholinesterase (AChE) activity. These
improvements suggest that Aloe barbadensis confers neuroprotection through its diverse phytochemicalssuch
as acemannan, which boosts immune response and scavenges free radicals, beta-sitosterol which binds
acetylcholinesterase and butyrylcholinesterase, improving cholinergic function[10], aloinand aloe-emodin,
which inhibits lipid peroxidation and reduce neuroinflammation. These phytochemicals are known to neutralize
free radicals, regulate inflammatory responses, and promote neuronal survival ([7],[3]).
Histological evaluations using H&E and Silver Bielschowsky staining further validated the extract’s protective
role. Mercury exposure resulted in pyknotic nuclei, reduced neuronal density, and mild plaque formation
features reminiscent of Alzheimer’s disease. In contrast, rats treated with Aloe barbadensis showed preserved
brain architecture and minimal or absent neurofibrillary tangles and senile plaques. These findings are consistent
with studies indicating that plant-derived antioxidants can suppress amyloid plaque formation and tau protein
hyperphosphorylation—two key pathological processes in Alzheimer’s progression ([9],[20]).
Emerging research also suggests that compounds in Aloe barbadensis may exert their effects by modulating
multiple neuroprotective pathways, including ApoE4/LRP1, Wnt/β-catenin, and TLR4/NLRP3 signaling. These
pathways are involved in neuroinflammation, synaptic regulation, and amyloid clearance, further supporting
Aloe’s potential as a multi-targeted therapeutic agent for neurodegenerative conditions [9].
In broader context, reviews of medicinal plants in Alzheimer’s therapy highlight Aloe barbadensis as a promising
herb for reducing oxidative damage and preserving cognitive function. Reference[21] emphasized Aloe’s role in
enhancing synaptic plasticity and mitigating neuroinflammation, while [4] advocated for the integration of
African phytochemicals like Aloe into Alzheimer’s treatment strategies due to their accessibility, affordability,
and diverse mechanisms of action.
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CONCLUSIONS
This study provides compelling evidence that the ethanolic extract of Aloe barbadensis effectively mitigates
mercury-induced Alzheimer-like alterations in the basal ganglia of Wistar rats. Across behavioral, biochemical,
and histological domains, the extract demonstrated a robust capacity to reverse neurotoxic damagereducing
anxiety, enhancing memory, restoring antioxidant enzyme activity, and preserving neuronal integrity.
The significance of these findings lies in the extract’s ability to counteract hallmark features of
neurodegeneration, including oxidative stress, cholinergic dysfunction, and the formation of senile plaques and
neurofibrillary tangles. These pathological markers are central to Alzheimer’s disease, and their attenuation by
Aloe barbadensis suggests that the plant’s bioactive compoundssuch as acemannan, aloinand aloe-emodin
may modulate key neuroprotective pathways.
Given its accessibility, affordability, and multi-targeted therapeutic potential, Aloe barbadensis emerges as a
promising natural agent for managing heavy metal-induced neurotoxicity and Alzheimer-like symptoms. Its
integration into preventive or adjunctive strategies could offer a safer, plant-based alternative in the broader
context of neurodegenerative disease management.
Suggestions for Further Research
While this study highlights the neuroprotective potential of Aloe barbadensis against mercury-induced damage,
further research is warranted to deepen our understanding of its therapeutic mechanisms. Future studies should:
Investigate the molecular pathways involved in Aloe’s antioxidant and anti-inflammatory effects, including
its influence on tau phosphorylation, amyloid clearance, and neuroinflammatory signaling.
Explore dose-response relationships and long-term safety profiles to determine optimal therapeutic
windows.
Conduct clinical trials to assess its efficacy in human populations, particularly in individuals at risk for
heavy metal exposure or neurodegenerative conditions like Alzheimer’s disease.
Utilize advanced techniques such as gene expression profiling, proteomics and immunohistochemistry to
validate its effects at the cellular and molecular levels.
These directions will help translate the promising results of this study into practical applications for
neuroprotective therapy.
ACKNOWLEDGMENT
Special thanks to all the works cited which served as the basis for this work.
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